title: Cardiotrophin-1 administration protects from ischemia-reperfusion renal injury and inflammation.
abstract: BACKGROUND
  Ischemia-reperfusion injury (IRI) remains a major problem in renal transplantation, and the inflammatory response to IRI exacerbates the resultant renal injury. We have investigated whether the systemic administration of cardiotrophin-1 (CT-1) is able to improve renal function and to decrease inflammatory responses in a rat model of renal IRI.
  
  
  METHODS
  IRI was induced by renal pedicle clamping (60 min) followed by reperfusion and contralateral nephrectomy. CT-1 was injected through the penile vein 30 min before clamping release and its effects were compared with a saline-treated group at five different time points of reperfusion.
  
  
  RESULTS
  Survival in the CT-1-treated group was higher than in the untreated group and prevented IRI-induced reduction in the glomerular filtration rate, as shown by blunted increases in creatinine and urea plasma levels and less severe decrease in creatinine clearance. These effects of CT-1 seem to be mediated by reduction in oxygen-radical production, increased superoxide dismutase expression, attenuation of neutrophil and macrophage infiltration, lower adhesion molecule expression, lower inflammation demonstrated by a decrease of plasma levels of proinflammatory cytokine secretion such as tumor necrosis factor-α, interleukin-1β and interferon-γ, lower inducible nitric oxide synthase expression and lower nuclear factor-κB activation, and reduced apoptosis.
  
  
  CONCLUSIONS
  Therefore, these results suggest that CT-1 administration prevents IRI and it might be used as a therapeutic strategy to protect the kidney against IRI.
authors.affiliation: 1 Department of Surgery, University of Salamanca, Salamanca, Spain. 2 Biosanitary Research Institute (IBSAL), Salamanca Spain. 3 Digna Biotech, Madrid, Spain. 4 Department of Nephrology, Hospital del Mar, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. 5 Renal and Cardiovascular Physiopathology Unit, Department of Physiology and Pharmacology, University of Salamanca, Salamanca, Spain. 6 Queen Sofía Institute for Renal Research, Renal Foundation, Madrid, Spain. 7 Address correspondence to: José M. Lopez-Novoa Ph.D., Renal and Cardiovascular Physiopathology Unit, Department of Physiology and Pharmacology, University of Salamanca, Edificio Departamental, Campus Unamuno, 37007 Salamanca, Spain.
authors.forename: María B
authors.initials: MB
authors.lastname: Garcia-Cenador
authors.forename: María F
authors.initials: MF
authors.lastname: Lorenzo-Gomez
authors.forename: Julio J
authors.initials: JJ
authors.lastname: Herrero-Payo
authors.forename: Juan
authors.initials: J
authors.lastname: Ruiz
authors.forename: María P
authors.initials: MP
authors.lastname: Perez de Obanos
authors.forename: Julio
authors.initials: J
authors.lastname: Pascual
authors.forename: José M
authors.initials: JM
authors.lastname: Lopez-Novoa
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Garcia-Criado
mesh_terms: D000818:Animals; D017209:Apoptosis; D016207:Cytokines / Q000008:administration & dosage*; D007249:Inflammation; D007371:Interferon-gamma / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007668:Kidney / Q000473:pathology*; D016030:Kidney Transplantation / Q000379:methods*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D015427:Reperfusion Injury / Q000473:pathology* / Q000517:prevention & control; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D007371:Interferon-gamma; C092073:cardiotrophin 1; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D013482:Superoxide Dismutase